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Improving selection of patients with metastatic colorectal cancer to benefit from cetuximab based on KIR genotypes
Entity
UAM. Departamento de MedicinaPublisher
BMJ Publishing Group LtdDate
2021-04-01Citation
Journal For Immunotherapy Of Cancer 9.4 (2021): e001705ISSN
2051-1426Funded by
This study was funded by Merck SL, an affiliate of Merck KGaA, Darmstadt, Germany (research project number 2010-023580-18, date: June 5, 2014). BM-M is a recipient of a contract from Programa Operativo Fondo Social Europeo 2014-2020 (D1113102S1) and Consejería de Salud y Familias Junta de Andalucía (HR-0060-2020)Editor's Version
https://doi.org/10.1136/jitc-2020-001705Subjects
Tumor; Biomarkers; Neoplasm; Natural Killer T-Cells; Translational Medical Research; Antibodies; MedicinaRights
© Author(s) (or their employer(s)) 2021Abstract
Aim Cetuximab is a standard-of-care treatment for KRAS wild-type metastatic colorectal cancer (mCRC), but it may also be effective in a subgroup of KRAS mutant patients by its immunomodulatory activity. Here, we explore if KIR (killer cell immunoglobulin-like receptor) genotyping can provide a significant added value in the clinical outcome of patients with KRAS mutant mCRC based on cetuximab treatment.
Methods We included 69 patients with histologically confirmed mCRC and KRAS mutation, positive EGFR expression, and Eastern Cooperative Oncology Group performance status ≤2. Based on KIR gene content, haplotype (A or B) was defined and genotypes (AA or Bx) were grouped for each patient.
Results We demonstrated with new evidence the immunomodulatory activity of cetuximab in patients with KRAS mutant mCRC. Patients with homozygous genotypes (AA or BB) showed shorter 12-month progression-free survival (PFS12) and poorer overall survival (OS) than those with heterozygotes (AB). Moreover, multivariate analysis confirmed stratification of patients based on genotype was an independent marker of PFS12 (HR 2.16) and the centromeric and telomeric distribution of KIRs was an independent predictor of both PFS12 (HR 2.26) and OS (HR 1.93) in patients with mCRC with KRAS mutation treated with cetuximab.
Conclusions Selection of patients with mCRC based on their KIR genotypes opens a therapeutic opportunity for patients with KRAS mutation, and it should be tested in clinical trials in comparison with other alternatives with scarce benefit.
Trial registration number NCT01450319, EudraCT 2010-023580-18
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Google Scholar:Manzanares-Martin, Bárbara
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Cebrián Aranda, Arancha
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Puerto Nevado, Laura del
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González, Rafael
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Solanes, Sonia
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Gómez-España, Maria Auxiliadora
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García-Foncillas López, Jesús Miguel
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Aranda, Enrique
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